Method for delivery of pharmaceuticals for treating or preventing presbyopia

ABSTRACT

Embodiments of the present invention relate to a method for delivering pharmaceuticals to the lens of the eye to treat or prevent presbyopia. According to the embodiments, pharmaceuticals may be applied by providing the pharmaceuticals to the eye and promoting delivery of the pharmaceuticals into the lens capsule and/or lens fibers of the lens of the eye. Methods include iontophoresis, nano-medication, and photonic activation to deliver the pharmaceuticals to treat or prevent presbyopia.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.10/050,879, filed Jan. 18, 2002 now U.S. Pat. No. 6,923,955. Thisapplication also claims the benefit under 35 U.S.C. 119(e) ofprovisional application No. 60/574,211, filed May 26, 2004. U.S.application Ser. No. 10/050,879 is a continuation-in-part of U.S.application Ser. No. 09/930,287, filed Aug. 16, 2001 and now abandoned,and claims the benefit under 35 USC 119(e) of provisional applicationNo. 60/262,423, filed Jan. 19, 2001. U.S. application Ser. No.09/930,287 claims the benefit under 35 USC 119(e) of provisionalapplication No. 60/225,659, filed Aug. 16, 2000.

FIELD OF THE INVENTION

The present invention relates to methods for delivering pharmaceuticalsfor treating or preventing presbyopia. These methods may include usingchemical or mechanical systems to deliver the pharmaceuticals.

BACKGROUND

Presbyopia affects virtually every person over the age of 44. Accordingto Jobson Optical Database, 93% of people 45 and over are presbyopic.Presbyopia entails the progressive loss of amplitude of accommodationthat occurs with aging. Adler's Physiology of the Eye, which isincorporated herein by reference, discloses that the human accommodativeamplitude declines with age such that accommodation is substantiallyeliminated by the age of 50 to 55. Accommodative ability, as defined byU.S. Pat. No. 5,459,133 to Neufeld and incorporated in its entiretyherein by reference for background information, is the capacity of theeye to focus for near vision by changing the shape of the lens to becomemore convex.

The ocular tissues involved in the accommodative response include thelens, the zonules, the lens capsule, and the ciliary muscle. Of these,the lens is the central tissue. These structures function together toenable the eye to focus on close objects by changing the shape of thelens. The lens is centrally suspended between the anterior and posteriorchambers behind the pupillary opening of the iris. The lens is supportedby an array of radially oriented zonular fibers, which extend from thelateral edges of the lens to the inner border of the circumferentialciliary muscle. The ciliary muscle is attached to the scleral coat ofthe eye. When the eye is at rest, it is focused for distance and thelens is in a somewhat flattened or less convex position. This shape isdue to the tension that is exerted on the lens periphery by the zonules.The zonules pull the edges of the lens toward the ciliary body.

During accommodation, the shape of the lens becomes more convex throughcontraction of the ciliary muscle, which allows the ciliary attachmentof the zonules to move toward the lens, reducing the tension in theanterior zonules. This reduction in tension allows the central region ofthe lens to increase in convexity, thereby enabling near objects to beimaged on the retina. The processes involving the coordinated effort ofthe lens, zonules, ciliary body, medial rectus muscles and iris, amongothers, that leads to the ability of the eyes to clearly focus near onthe retina is the accommodative process.

Several theories have been advanced to explain the loss of accommodationwith age. These theories include the hardening of the lens with age,loss of strength in the ciliary muscle, factors related to the physicalgrowth of the lens, and, the loss of elasticity of the lens capsule. Asfor the loss of strength of the ciliary muscle, it is noted thatalthough there are age-related morphological changes that occur, thereis little evidence of diminishing strength of the ciliary muscle. Infact, under the influence of pilocarpine, the ciliary muscle willvigorously contract even in presbyopic eyes.

The lens grows throughout one's life and theories have been proposedthat it is this increase in size that prohibits the effects of thezonules from affecting a change in the shape of the lens. Recent worksexploring this possibility have not met widespread acceptance thus far.Most of the growth of the lens is not in its diameter, but instead, inits anterior-posterior dimensions.

As for changes in the lens capsule, it has been postulated thatreduction in the elasticity of the capsule is, in fact, a contributingfactor in presbyopia. Moreover, it has been found that Young's modulusof elasticity for the lens capsule decreases by nearly 50% from youth toage 60, while accommodation decreases by 98%. Consequently, theprincipal cause of presbyopia is now considered to be “lenticularsclerosis” or the hardening of the lens.

A cataract is a condition in which the lens becomes less clear. Thestudy of cataracts lends insight into lens and capsular changes. Theusual senile cataract is relatively discus-shaped when removed from theeye, its shape being dictated by the firm lens substance. The liquefiedhypermature cataract is globular when extracted, rounded up by theelastic lens capsule. This is indirect evidence that it may be possibleto reverse the lenticular changes associated with presbyopia, and thatthe lens capsule is still sufficiently elastic.

At the present time, common treatments for presbyopia include readingglasses, bifocal glasses, or mono-vision contact lenses. All of thesesolutions necessitate the use of an appliance creating additionalshortcomings.

Alternative theories for treating presbyopia include scleral expansionand corneal reshaping. The efficacy of such techniques is notwell-established and, importantly, these techniques do not attempt toreverse what the inventors of the subject-application believe to be asubstantial causation, as explained more fully below, in the loss of theaccommodative amplitude of the lens typically associated with the normalaging process. Moreover, because scleral expansion and corneal reshapinginvolve macroscopic changes in the morphology of the lens and/or corneait fails to reverse presbyopia.

Finally, the use of the excimer laser for the purposes of cornealreshaping to produce a multifocal refracting surface has been disclosedin U.S. Pat. No. 5,395,356. While this method seems promising, it stillrequires structural changes to the cornea to compensate for agingchanges in the lens. Rather than trying to undo the changes brought onby presbyopia, techniques such as these merely compensate for the lossof accommodative function by altering another ocular structure.

SUMMARY OF THE INVENTION

While not wishing to be bound to any particular theory, it is nowbelieved that presbyopia is caused by the hardening of the lens, whichcan be due to an alteration of the structural proteins or an increasedadhesion between the lens fibers. It is also believed that theintralenticular viscosity increases with age as a result of theformation of certain chemical bond structures within the lens.Accordingly, the present invention includes methods and apparatus forpreventing and/or treating presbyopia through treatment of the lens suchthat the viscosity of the lens is reduced, thereby restoring theelasticity and movement to the lens fibers and increasing theaccommodative amplitude of the lens.

Embodiments of the present invention also include methods of treatingpresbyopia resulting in underlying changes in the structures and/orinteractions of molecules comprising those components of the eyeassociated with the accommodative process, most notably the lens and/orlens capsule.

In an embodiment, a novel molecular approach to treating presbyopia byrestoring the accommodative amplitude of the lens is provided. Inanother embodiment, treating presbyopia while also reducing the tendencyfor the lens to lose its restored accommodative amplitude is provided.

In another embodiment, the onset of presbyopia is prevented by regularlyadministered treatment where elasticity and the accommodative ability ofthe lens is restored. By applying the treatments as described herein tothe eyes of persons in their mid to late 30's, or even younger, theon-set of presbyopia, as defined by a loss of accommodation, such thatthe accommodative power of the eye is below 2.5 Diopters, can beavoided. Such treatments whether for the purposes of preventing ortreating presbyopia, would be occasionally repeated during the course ofa patient's lifetime. The frequency of the treatment would be determinedby the degree of accommodative loss that needs to be recovered, theamount of accommodation that can be safely restored in a singleprocedure, and the amount of restoration desired.

In one embodiment, a method for treating presbyopia by breakingdisulfide bonds in molecules comprising the structures of the eye, mostnotably the lens and the lens capsule is provided. Disulfide bonds arebelieved to be a substantial factor in the progressive loss ofaccommodative amplitude. In another embodiment, the breaking of thedisulfide bonds is accompanied by chemical modification of the sulfurmoiety in the cysteine molecule formed upon breaking of the disulfidebonds, such chemical modification rendering the sulfur moiety lesslikely to form new disulfide bonds. This method thus comprises a methodfor preventing, and/or reducing the recurrence of presbyopia by reducingthe probability of forming new disulfide bonds. Particularly, thisaffects a change in the accommodative amplitude of the human lens by:(1) using various reducing agents that cause a change in theaccommodative abilities of the human lens, and/or (2) the use of appliedenergy to affect a change in the accommodative abilities of the humanlens. It is believed that by breaking bonds, such as disulfides, thatcrosslink lens fibers together and increase lens viscosity causing ahardening of the lens cortex and lens nucleus, this increases theelasticity and the distensibility of the lens cortex, lens nucleus,and/or the lens capsule.

Presbyopia, or the loss of the accommodative amplitude of the lens, hasoften advanced in a typical person age 45 or older to the point wheresome type of corrective lens in the form of reading glasses or othertreatment is required. It is to be understood that loss of accommodativeamplitude can occur in persons much younger or older than the age of 45,thus the present invention is not to be construed as limited to thetreatment of presbyopia in a person of any particular age. The presentinvention is most useful in a person whose accommodative amplitude haslessened to a point where restoration thereof to some degree isdesirable. However, the invention should not be limited to thecorrection of presbyopia, but may be used to prevent presbyopia fromoccurring.

In one embodiment, the method of treating or preventing presbyopia willresult in an increase in the accommodative amplitude at least about by0.5 diopters. In another embodiment, the method of treating orpreventing presbyopia will result in an increase in the accommodativeamplitude of at least about 2.0 diopters. In still another embodiment,the method of treating or preventing presbyopia of the present inventionwill result in an increase in the accommodative amplitude by at leastabout 5 diopters. In another embodiment of the present invention, themethod of treating or preventing presbyopia of the present inventionwill result in an increase of the accommodative amplitude of the lens torestoration thereof to that of a lens with a normal accommodativeamplitude of 2.5 diopters or greater. It is noted that while it isobviously most beneficial to restore the accommodative amplitude of thelens to a normal accommodative amplitude, lesser degrees of restorationare also beneficial. For example, in some cases advanced presbyopia cancause severe reduction in the accommodative amplitude, thus making acomplete restoration of the amplitude improbable.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an iontophoretic device that may be used with methodsaccording to embodiments of the present invention.

FIG. 2 is a flowchart of a method for delivering pharmaceuticals byphotonic activation.

DETAILED DESCRIPTION

The accommodative amplitude of the lens is measured in diopters (D). Theloss of accommodative ability begins at a very early age, such that byage 10 the average eye has 10 D, age 30, 5 D, and by age 40, only 2.5 Dof accommodative power. The lens of a person who does not suffer frompresbyopia (i.e. a person whose lens accommodates normally), willtypically have an accommodative amplitude of about 2.5 diopters orgreater. The terms “treating presbyopia” as used herein mean increasingthe accommodative amplitude of the lens.

As stated, inelasticity of the lens, or hardening thereof, is believedto be a contributing cause of presbyopia. The hardening of the lens canbe due to an alteration of the structural proteins or an increasedadhesion between the lens fibers. Additionally, it is believed that thelens viscosity also increases with age due to an increased concentrationof certain chemical bond structures within the lens. In one embodiment,presbyopia may be treated by altering the molecular and/or cellularbonds between the cortical lens fibers so as to free their movement withrespect to each other. The increased elasticity of the lens apparatuscan restore lost amplitude of accommodation. Specifically, it isbelieved that disulfide bonds in the molecules comprising the structuresof the eye responsible for proper accommodation are a substantial factorin the hardening of the lens and the concomitant loss of accommodativeamplitude.

Thus, in one embodiment, the process may involve breaking the disulfidebond and then protonating the newly formed sulfur moiety with a reducingagent such as glutathione to impart a hydrogen atom thereto. The stepscan be performed simultaneously or consecutively. In either case, thereducing agent can be present at the time the disulfide bond is brokenin order to eliminate reformation of disulfide. That is, the reducingagent can introduce and bond a moiety onto the free sulfur afterbreaking the disulfide bond such that the likelihood of reformation ofanother disulfide bond is prevented or at least reduced. While thereducing agent may introduce a hydrogen atom onto the free sulfur, thusforming a sulfhydryl group (—SH), the resultant —SH groups can again beoxidized to form a new disulfide bond. Thus, it is advantageous tointroduce a group into the free sulfur moiety, such as lower alkyls,methylating compounds, or other agents, which reduce the tendency of newdisulfide bond formation. This method can result in a substantialprevention of the reoccurrence of presbyopia.

As stated, it is believed that the disulfide bonds form both between thelens fibers, between lens proteins, and between lens proteins andvarious thiols both within and on lens fibers. These bonds andsubstantially reduce the lens fibers' ability to easily move relative toeach other and thus the ability of the lens to accommodate properly.While not wishing to be bound by any particular theory, the bonds mayform by way of absorption of light energy, which causes the sulfhydrylbonds on the lens proteins to oxygenate removing a hydrogen atom fromtwo adjacent —SH groups and creating water and a disulfide bond.Reducing the disulfide bonds requires hydrogen donors such asglutathione or other molecules. Other possible theories involveprotein-thiol mixed disulfide bonds forming such asprotein-S—S-glutathione or protein-S—S-cysteine. Glutathione thereforemay be both part of the solution and part of the problem. The use ofGlutathione in any treatment regimen, therefore, must be monitoredcarefully in light of the potential for an increase in undesirable bondformation.

The total refractive power of the lens is greater than what would beexpected based on the curvature and the index of refraction. As stated,contraction of the ciliary muscle causes the ciliary body to moveforward and towards the equator of the lens. This causes the zonules torelax their tension on the lens capsule, which allows the central lensto assume a more spherical shape. During accommodation, the main changeis in the more central radius of curvature of the anterior lens surface,which is 12 mm in the unaccommodative state and can be 3 mm centrallyduring accommodation. Both the peripheral anterior and the posteriorlens surfaces change very little in curvature during accommodation. Theaxial thickness increases while the diameter decreases. The centralanterior lens capsule is thinner than the rest of the anterior capsule.This may explain why the lens bulges more centrally duringaccommodation. The thinnest portion of the capsule is the posteriorcapsule, which has a curvature greater than the anterior capsule in theunaccommodative state. The protein content of the lens, almost 33% byweight, is higher than any other organ in the body. There are manychemical compounds of special interest in the lens. For example,glutathione is found in high concentration in the lens cortex eventhough there is very little in the aqueous. Thus, the lens has a greataffinity for glutathione and actively absorbs, transports andsynthesizes glutathione. Approximately 93% of intralenticularglutathione is in the reduced form. Glutathione may be involved withmaintaining the lens proteins, the sulfhydryl groups (—SH), in theirreduced states. That is, after the disulfide bond is broken and thesulfur moieties are made available, glutathione can impart a hydrogenatom to form the sulfhydryl group thereby preventing or minimizing thereformation of a disulfide bond. In addition, ascorbic acid can also befound in very high concentrations in the lens. It is activelytransported out of the aqueous and is at concentrations 15 times thatfound in the bloodstream. Both inositol and taurine are found at highconcentrations in the lens for which the reason is not known.

According to one embodiment, the increase in the accommodative amplitudeis accomplished by treatment of the outer lens region (the cortex) orthe inner layer (the nucleus) with radiation, sonic or electromagneticenergy, heat, chemical, particle beam, plasma beam, enzyme, genetherapy, nutrients, other applied energy source, and/or any combinationof any of the above sufficient to break the disulfide bonds believedresponsible for the inelasticity of the lens. Chemicals are useful toreduce disulfide bonds that are believed to anchor lens fibers hencepreventing their free movement and elasticity. By making the anteriorcortex and/or the nucleus more elastic, viscosity is lowered and thelens is again able to assume its characteristic central bulge duringaccommodation.

Chemicals suitable for causing reduction include, by way of exampleonly, glutathione, ascorbic acid, Vitamin E, tetraethylthiuram disulfyl,i.e., reducing agent, any biologically suitable easily oxidizedcompound, ophthalmic acid, inositol, beta-carbolines, any biologicallysuitable reducing compound, reducing thiol derivatives with thestructure:

or sulfur derivatives with the structures:

wherein R₁, R₂, R₃ and R₄ are independently a straight or branched loweralkyl that may be substituted, e.g., by hydroxyl, lower alkoxy or loweralkyl carbonyloxy, their derivatives or a pharmaceutically acceptablesalt thereof. Preferred exemplary reducing agents include diethyldithiocarbamate, 1-methyl-1H-tetrazol-5-yl-thiol and1-(2-hydroxyethyl)-1H-tetrazol-5-yl-thiol or and pharmaceuticallyacceptable salts thereof. Other useful compounds can be found in U.S.Pat. No. 5,874,455, which is hereby incorporated in its entirety byreference for background information. The above-mentioned chemicals aremerely exemplary and other reducing agents that behave similarly bybreaking the disulfide bond are included within the scope of thisinvention.

The chemical reducing agents can be used alone or in conjunction with acatalyst such as an enzyme. Enzymes and other nutrients suitable forcausing or facilitating reduction include, for example, aldoreductase,glyoxylase, glutathione S-transferase, hexokinase, thiol reductase,thioltransferase, tyrosine reductase or any compatible reductase. Theneed for a source of applied energy for the reduction of the disulfidebonds may be met by the addition of glucose-6-phosphate, which ispresent within the lens but the enzyme, hexokinase that normallyconverts the glucose to the G6P energy state is rendered non-functionalby the process of thiol oxidation. Again, it should be noted that theabove-listed enzymes are exemplary and not an exhaustive list. Theenzymes can be naturally present in the eye, or can be added to the eyetogether with or separate from the chemical reducing agent or energeticmeans disclosed herein. As such, other chemically and biologicallycomparable enzymes that help break disulfide bonds or behave similarlyshould be considered as within the scope of the present invention.

In one embodiment, the reduction of disulfide groups of the lensproteins to sulfhydryl groups is accomplished by delivering to the lensa compound such as glutathione, thiols, or others in sufficientquantities to reduce the disulfide bonds and other molecular andcellular adhesions. Other enzymes or chemicals that affect a methylationon the free sulfur atom include for example, methyl-methanethiosulfonate, methyl glutathione, S-methyl glutathione, S-transferaseand other biologically compatible methylating agent. Use of emulsionssuch as nanocapsules, albumin microspheres, carrier molecules such asinositol, taurine or other biologically suitable means such as virusphages for delivering the reducing agent or enzymes to the lens is anintegral part of this invention. The chemical reducing agent willtypically be delivered in the form of a solution or suspension in anophthalmically acceptable carrier. In some cases, the application ofenergy to affect or catalyze the reduction of the disulfide bonds aswell as the disruption of other bonds and adhesions may be beneficial.The application of energy alone can be used to break the disulfidebonds. Applied energy can have any form, by way of example only, any oflaser, ultrasound, particle beam, plasma beam, X-ray, ultraviolet,visible light, infrared, heat, ionizing, light, magnetic, microwave,sound, electrical, or other not specifically mentioned, can be usedalone or in combination with the reducing agents to affect the treatmentof presbyopia, or a combination of any of these types of energies.

In a similar manner, agents can be delivered to the lens capsule, whichbind or interact with the capsule to affect greater elasticity ordistensibility. Such agents either cause the capsule to shrink insurface area or increase the tension of the lens capsule on theperipheral anterior or posterior of the lens. Applied energy can haveany form, by way of example only, any of laser, ultrasound, heat,particle beam, plasma beam, X-ray, ultraviolet, visible light, infrared,ionizing, light, magnetic, microwave, sound, electrical, or other notspecifically mentioned can be used alone or in combination with thereducing agents to affect the treatment of presbyopia or a combinationof any of these types of applied energy.

In another embodiment, applied energy can be used as a catalyst toinduce or increase the rate of the reduction reaction. Thus, by applyingenergy, the peripheral portion of the capsule is preferentiallyaffected, leaving the central 4 mm zone of accommodation unaffected.This allows the lens to assume a more accommodative state. The appliedenergy can also be applied alone to promote the reduction reaction andthe cellular changes that ultimately affect the lens' cortex. Asexamples, lasers useful in the present invention include: excimer, argonion, krypton ion, carbon dioxide, helium-neon, helium-cadmium, xenon,nitrous oxide, iodine, holmium, yttrium lithium, dye, chemical,neodymium, erbium, ruby, titanium-sapphire, diode, femtosecond orattosecond laser, any harmonically oscillating laser, or any otherelectromagnetic radiation. Exemplary forms of heating radiation include:infrared, heating, infrared laser, radiotherapy, or any other methods ofheating the lens. Finally, exemplary forms of sound energy that can beused in an embodiment of the invention include: ultrasound, any audibleand non-audible sound treatment, and any other biologically compatiblesound energy.

In still another embodiment, radiation, such as ultraviolet light,visible light, infrared, microwave, or other electromagnetic energy maybe placed in the eye to help break the disulfide bonds. This would thenmake it possible for the reduction of the disulfide bonds to occur.

The applied energy used with various embodiments and methods of thepresent invention could be applied through either contact with thesclera or cornea, non-contact techniques, or through intraocular methodsof delivery. More than one treatment may be needed to affect a suitableincrease in the accommodative amplitude. When more than one modality oftreatment is desirable, chemical treatment can be administered prior to,after, or simultaneously with the application of energy.

Embodiments of the present invention further relate to methods fordelivering pharmaceuticals to the lens of the eye for treating orpreventing presbyopia. These methods may provide delivery of effectiveamounts of pharmaceuticals directly into the lens capsule and/or thelens fibers to break down disulfide bonds at the lens fibers and preventthese bonds from forming, thereby treating or preventing presbyopia.

In one embodiment, iontophoresis may be used to deliver thepharmaceutical. FIG. 1 illustrates an iontophoretic device that may beused according to methods of the present invention. Iontophoretic device100 may include a controller 110, which may include logic, a voltagesource, and other electrical components to control and deliver anelectric current. Electrodes 120 may be electrically attached to thecontainer to transmit and receive the electric current. Electrodes 120may have conductive pads 130 for contacting and/or attaching to humantissue. As further described below, the pads 130 may be directlyattached to the head and/or face prior to the beginning of delivery ofthe pharmaceuticals.

Iontophoresis involves applying an electric current to a chargedsubstance to facilitate the delivery of the charged substance into humantissue. Iontophoretic electrodes 120 may be spaced apart near thelocation for the charged substance to be delivered. Applying an electriccurrent between the electrodes creates an electric field whereby thecharged substance travels via the electric field through the tissue.

In this embodiment, any of the pharmaceuticals as described above mayfirst be added to a solution that is placed in a charged state by anymethod for ionizing solutions. The charged solution may then beadministered to the eye by eye drops, eye swabs, or any other suchmethod. The electrodes may be placed at various locations on the face orhead in order to establish an electric field through the lens area ofthe eye. The electric current may be applied by the electrodes. Thecharged solution may then travel in the direction of one of theelectrodes. The charged solution is drawn into the eye toward the lens,across the lens membrane, through the lens, and/or into the lens fibersand/or lens capsule by the electric field. After the pharmaceutical isdelivered, the electric current may be turned off.

In another embodiment, nano-medication may be used to deliverpharmaceuticals for treating or preventing presbyopia. Nano-medicationinvolves the delivery of pharmaceuticals in such small forms, on theorder of nanometer size, such that the pharmaceutical molecules easilydiffuse through the capillaries of the eye into the lens and lens fibersand/or lens capsule.

In this embodiment, any of the pharmaceuticals as described above mayfirst be processed to form nanometer sized molecules. These moleculesmay be formed into nano-micelles, which may be a nanometer-sizedaggregation of the molecules, and encapsulated to prevent interactionprior to arrival at the desired location in the body. The nano-micellesmay be administered to the eye as eye drops, eye swabs, or any othersuch method. Upon contact with the eye, the capillaries of the eye mayreadily absorb the nano-micelles containing the pharmaceutical anddistribute the pharmaceutical across the lens membrane, through thelens, and/or into the lens fibers and/or lens capsule.

Upon arrival at the lens fibers and/or lens capsule, the nano-micellecapsule may dissolve and the released pharmaceutical may have atherapeutic effect on the lens fibers and/or lens capsule.

In another embodiment, photonic activation may be used to deliverpharmaceuticals for treating or preventing presbyopia. In thismechanism, photons may be directed to an inert substance, therebyactivating the substance. Photons may be applied by a laser, an LED, orany other incoherent light source.

FIG. 2 is a flowchart of a photo activation method for deliveringpharmaceuticals for treating or preventing presbyopia. The inertsubstance may be administered to and dispersed (210) into human tissue.After the substance arrives (215) at the desired location in the body,photons may then be directed (220) to the inert substance. Upon contactwith the photons, the inert substance may activate (230) so as to affectthe human tissue into which the substance dispersed. The inert substancemay include compounds that may be activated by selective wavelengths oflight, selective absorption of light, e.g., exogenous chromophores, andother such techniques.

In this embodiment, a pro-drug of any of the pharmaceuticals asdescribed above may be used. A pro-drug is a pharmaceutical that may beformulated in an inert state, i.e., being chemically structured so asnot to have a therapeutic effect, and then changeable from the inertstate to an active state to exert its effects. In its inert state, apro-drug may be able to penetrate human tissue more easily than it itsactive state because the drug may not interact with the penetratedtissue as the drugs contacts it. Hence, the inert pro-drug may be easierto deliver in effective amounts to a specific site in the tissue. Onceat the site, the pro-drug may be activated to generate its therapeuticeffect. In this embodiment, the pro-drug may be activated by photons.Activating the pro-drug may involve altering the chemical properties ofthe components of the pro-drug, e.g., breaking the chemical bonds of thepro-drug to form a different pharmaceutical substance with differentproperties.

The pro-drug may be administered to the eye as eye drops, eye swabs, orany other such method. The pro-drug may then be absorbed into the eyetoward the lens, across the lens membrane, through the lens, and/or intothe lens fibers and/or lens capsule. Photons may be then be directed tothe pro-drug, activating the pro-drug. The active pro-drug may thenperform its therapeutic function on the lens fibers and/or lens capsule.

Photons may be directed so as to provide a differential gradient ofactivation. That is, the pro-drug in one location of the eye may be moreactive than the pro-drug in another location of the eye by providingdifferent levels of photonic energy to those locations.

Several embodiments of the present invention are specificallyillustrated and described herein. However, it will be appreciated thatmodifications and variations of the present invention are covered by theabove teachings and within the purview of the appended claims withoutdeparting from the spirit and intended scope of the invention.

1. A method for delivering a pharmaceutical substance comprising:providing a pharmaceutical substance to an eye; and promoting deliveryof the pharmaceutical substance into the lens capsule and/or lens fibersof the eye, wherein promoting delivery comprises using iontophoresis tourge the substance, in a charged state, into the lens capsule and/or thelens fibers.
 2. The method of claim 1, wherein using iontophoresiscomprises: applying the substance, in the charged state, to the eye;applying an electric voltage to an area around the eye; forming anelectric field from the electric voltage through the lens of the eye,the electric field being large enough to urge the substance, in thecharged state, to the lens capsule and/or the lens fibers; anddiscontinuing the electric voltage.
 3. A method for nano-medicationcomprising: providing a nanometer-scaled pharmaceutical substance to aneye; and promoting delivery of the nanometer-scaled pharmaceuticalsubstance into the lens capsule and/or lens fibers of the eye.
 4. Themethod of claim 3, wherein the nanometer-scaled pharmaceutical substancecomprises encapsulated nano-micelles.
 5. A method for delivering apharmaceutical substance comprising: providing a pharmaceuticalsubstance to an eye; and promoting delivery of the pharmaceuticalsubstance into the lens capsule and/or lens fibers of the eye, whereinpromoting delivery comprises using photonic activation to activate aninert form of the substance in the lens capsule and/or the lens fibers.6. The method of claim 5, wherein using photonic activation comprises:applying the inert form of the substance to the eye, wherein thesubstance diffuses to the lens capsule and/or the lens fibers; andapplying photons to the inert form of the substance to activate theinert form of the substance.
 7. The method of claim 6, wherein applyingphotons comprises: applying different levels of photon energy todifferent areas of the lens capsule and/or the lens fibers to activatethe inert form of the substance to different activity levels.
 8. Themethod of claim 5, wherein using photonic activation includes supplyingphotons from a laser or an LED.
 9. The method of claim 1, furthercomprising breaking chemical bonds that crosslink lens fibers togetherthus increasing distensibility in the lens capsule and/or the lensfibers of the eye.
 10. The method of claim 1, wherein the pharmaceuticalsubstance is delivered to the lens capsule.
 11. The method of claim 1,wherein the pharmaceutical substance is delivered to the lens fibers.12. The method of claim 3, further comprising breaking chemical bondsthat crosslink lens fibers together thus increasing distensibility inthe lens capsule and/or the lens fibers of the eye.
 13. The method ofclaim 3, wherein the pharmaceutical substance is delivered to the lenscapsule.
 14. The method of claim 3, wherein the pharmaceutical substanceis delivered to the lens fibers.
 15. The method of claim 5, furthercomprising breaking chemical bonds that crosslink lens fibers togetherthus increasing distensibility in the lens capsule and/or the lensfibers of the eye.
 16. The method of claim 5, wherein the pharmaceuticalsubstance is delivered to the lens capsule.
 17. The method of claim 5,wherein the pharmaceutical substance is delivered to the lens fibers.